Hypertension is a leading cause of cardiovascular disease and myocardial infarction (MI), and these are strongly associated with renal injury. However, the impact of MI additional to the effect of hypertension on renal injury is not clearly described. Further, while mineralocorticoid blockade with spironolactone (SP) has been shown to reduce cardiac fibrosis and improve cardiac re-modelling post MI; its effects on the kidney are unknown. We aimed to explore the effects of SP on renal fibrosis in hypertensive rats post MI.

Methods: Adult male transgenic Cyp1a1Ren2 rats were divided initially into two groups, normotensive (N) and hypertensive (H), and each further divided into five experimental groups: control animals, animals fed SP daily (50 mg.day-1) (+SP), animals that underwent sham operation (as a surgical control) (sham), animals with surgically induced MI (permanent left anterior coronary ligation) (+MI) and animals with surgically induced MI with additional daily administration of SP (+MI+SP). Hypertension (>160 mmHg systolic) was induced by addition of 0.167 % (w/w) indole-3-carbinol to the rat chow. Systolic blood pressure (SBP), urine collection and echocardiograms were recorded every four weeks. Cardiac and renal tissues were harvested for analysis either one month or three months.

Results: SBP was lower in the H+MI group (p=0.05) compared with the other H groups (155 ± 24 and 173 ± 11mmHg respectively). SBP was not significantly reduced by SP in either of the treated groups. Ejection fraction (EF) was significantly (p<0.001) reduced by MI induction, but not improved by SP treatment in both N and H groups. Glomerulosclerosis indices (GSI) were significantly raised in all hypertensive groups against normotensive values of 0.2 ± 0.1. SP significantly (p=0.002) decreased GSI in the H+SP group (0.9±0.04) from H controls (1.2 ± 0.07) and in the H+MI+SP (1 ± 0.1; p=0.04) from the H+MI group (1.3±0.1). The degree of renal cortical interstitial fibrosis in all hypertensive groups was not however modified by SP following one month, but did show a significantly slowed progression in induced hypertensive animals following three months.

Conclusion: Malignant hypertension produced extensive renal glomerulosclerosis and interstitial fibrosis over one month, which was increased further by three months. SP improved GSI scores, and reduced the extent of cardiac and renal fibrosis in hypertensive Cyp1a1Ren2 rats. No effect of SP administration was seen on SBP or cardiac EF. Further work will aim to better define the relationship between cardiac injury and renal damage.